The present invention relates to the stabilization of radiopharmaceutical preparations and to the stabilization of components of radiopharmaceutical kits. In particular, the present invention relates to stabilization of lyophilized components of radiopharmaceutical kits by the addition of a cyclic oligosaccharide, such as a modified or unmodified cyclodextrin, to the kit.
Modified cyclodextrins are known to be useful in stabilizing drugs. For example, U.S. Pat. No. 4,727,064 to Pitha describes pharmaceutical preparations consisting generally of a drug with a substantially low water-solubility and an amorphous, water-soluble complex of cyclodextrin. In particular, the Pitha patent describes (1) a method of converting drug compositions which are crystalline and of low water-solubility into intrinsically amorphous complexes which have improved pharmaceutical properties; and (2) the method comprising inclusion of multi-component mixtures of cyclodextrin derivatives in the drug compositions. Pitha points out that in order for the cyclodextrin derivatives to be effective in assisting dissolution of the drugs, that a substantial part of the drug molecule should fit into the hydrophobic cavity of the cyclodextrin molecule and the same part of the drug molecule should be hydrophobic. The method of Pitha is most directly concerned with stabilization of hormone compositions, such as testosterone, progesterone, and estrogenic drugs.
European Patent 149,197 to Brauns et al, also relates to ways of increasing the solubility of drug compositions which are sparingly water-soluble by themselves. Brauns et al particularly relates to pharmaceutical preparations containing such drug compositions and a partially etherified beta-cyclodextrin. Brauns et al also indicates that medicinal substances which exhibit the greatest increased water-solubility when converted to inclusion complexes with the beta-cyclodextrin are those having a corresponding fitting shape, i.e. they have to fit into the cavity of the beta-cyclodextrin cyclic system. Examples of such medicinal substances mentioned in Brauns et al, include non-steroidal antirheumatic agents, steroids, cardiac glycosides and derivatives of benzodiazepin, benzimidazole, piperidine, piperizine, imidazole, and triazole.
However, the prior art does not relate to stabilization of radiopharmaceutical preparations or to kits for forming radiopharmaceuticals. Further, the prior art relates only to formation of inclusion complexes wherein the drug fits within the framework of the modified cyclodextrin. Finally, the prior art does not relate to the stabilization of volatile components of a radiopharmaceutical kit.
Therefore, there remains a need to develop stabilization techniques for radiopharmaceutical kits.